Abstract: Objective: To investigate the effect of honokiol(HNK) on the inflammatory response in lung tissue of the asthma mice, and to clarify the intervention effect and its related mechanism. Methods: Twenty healthy female C57BL/6J mice were randomly divided into control group, model group, dexamethasone(DXM) group and HNK group,with 5 mice in each group.The asthma mouse model was established by intraabdominal injection of ovalbumin(OVA) combined with aluminum hydroxide[Al(OH)₃] suspension and OVA nasal stimulation.Thirty min before stimulation,the mice in DXM group and HNK group were treated with intraabdominal injection of the DXM solution and HNK solution, and the mice in model group were treated with the same amount of normal saline. After the mice were killed,the pathological changes of lung tissue were observed and evaluated by HE staining; the bronchoalveolar lavage fluid(BALF) was collected and the infiltration degree of inflammatory cells was observed by Diff-quik staining.The levels of IL-4,IL-6 and IL-17 in serum of the mice in various groups were detected by ELISA assay, and the expression levels of malondialdehyde(MDA) and the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in lung homogenate of the mice in various groups were detected by colorimetric method;the expression levels of p-JNK,nuclear factor-κB(NF-κB),Caspase-3,Bcl-2 and γH2Ax proteins in lung tissue of the mice in various groups were detected by Western blotting method.The immunofluorescence intensities of γH2Ax in lung tissue of the mice in various groups were measured. Results: Compared with control group, the number of airway epithelial exfoliation and necrosis cells of the mice in model group was increased obviously, the airway wall was thickened and the airway side inflammation cell infiltration degree was increased obviously;compared with model group,the performances mentioned above of the mice in DXM group and HNK group were alleviated;the pathological changes of lung tissue of the mice in HNK group were similar to DXM group.Compared with control group,the leves of IL-4, IL-6 and IL-17 in serum of the mice in model group were increased(P<0.05);compared with model group, the levels of IL-4,IL-6 and IL-17 of the mice in DXM group and HNK group were decreased(P<0.05);there were no significant differences in the IL-4, IL-6 and IL-17 levels in serum of the mice between HNK group and DXM group(P>0.05).Compared with control group,the level of MDA in lung homogenate of the mice in model group was increased(P<0.05),but the activities of SOD and GSH-Px were decreased(P<0.05);compared with model group,the levels of MDA of the mice in DXM group and HNK group were decreased(P<0.05),but the activities of SOD and GSH-Px were increased(P<0.05);there were no significant differences in the MDA levels and the activities of SOD and GSH-Px of the mice between HNK group and DXM group(P>0.05).Compared with control group, the expression levels of p-JNK,NF-κB,Caspase-3 and γH2Ax proteins in lung tissue of the mice in model group were increased(P<0.05),but the expression level of Bcl-2 protein was decreased(P<0.05); compared with model group, the expression levels of p-JNK,NF-κB,Caspase-3 and γH2Ax of the mice in DXM group and HNK group were decreased(P<0.05),but the expression levels of Bcl-2 protein were increased(P<0.05);there were no significant differences in the expression levels of p-JNK, NF-κB, Caspase-3, γH2Ax and Bcl-2 proteins in lung tissue of the mice between HNK group and DXM group(P>0.05).Compared with control group,the immunofluorescence intensity of γH2Ax in lung tissue of the mice in model group was significantly enhanced;compared with model group,the immunofluorescence intensities of γH2Ax in lung tissue of the mice in DXM group and HNK group were relatively weak,while the immunofluorescence intensity of γH2Ax in HNK group was similar to that in DXM group. Conclusion: HNK can inhibit the lung tissue injury and inflammation response in the asthma mice to a certain extent, and its mechanism may be related to its inhibition of oxidative stress and DNA damage.

Key words: honokiol, asthma, oxidative stress, DNA damage, dexamethasone